Tolerance

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Tolerance

• Tolerance refers to an
• antigen induced specific
• unresponsiveness

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Induction of tolerancean experiment of nature
Dizygotic twins in cows
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Experimental induction of tolerance
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The chimaeric mouse
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Factors affecting tolerancerole of antigen
Factors which affect response Favor immune response Favor tolerance
Physical form of antigen Route of injection Dose of antigen Large, aggregated, complex molecules, properly processed Subcutaneous or intramuscular Optimal dose soluble, aggregate-free, simple small molecules, not processed Oral or, sometimes, intravenous Very large or very small dose
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Factors affecting tolerancethe role of host
Factors that affect response Favor immune response Favor tolerance
Age of responding animal Differentiation state of cells Fully differentiated memory T B cells Older, immuno-logically mature Newborn (mice), immuno-logically immature Relative undifferentiated B cell with only IgM, T cells in the thymic cortex
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Immunologic features of tolerance

• It is an antigen-induced, active process
• Like immunologic memory, it is antigen specific
• Like immunologic memory, it can exist in B cells,
  T cells or both
• Like immunologic memory, its easier to induce and
  lasts longer in T cells than in B cell

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Tolerance in T and B cells
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High and low dose tolerance
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Host age and antigen dose affect tolerance
newborn
adult
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Mechanism of tolerance induction

• Clonal deletion
• Thymus negative selection
• Bone marrow IgM, IgD- B cells encountering
  self antigen
• Clonal anergy
• Lack of co-stimulatory(B7) molecules
• Exposure to large amounts of antigen
• Improper antigen presentation
• Lack of antigenic stimulus
• Receptor editing
• Anti-idiotype antibodies
• Suppressor T cells

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Clonal deletionnegative selection in the thymus
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Negative selection of B cells inbone marrow
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Clonal anergy in T cells
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Clonal anergy in B cells
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Tolerance due to lack of helper T cells
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Receptor editing among B cells
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Antiidiotype antibody in tolerance
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Breakdown of tolerance

• Immunosuppression
• Lack of antigen during differentiation of new
  clones
• Lack of antigen exposure
• As above
• Cross reactive antigens